Synthesis and evaluation of ent-Conduramine C-1 derivatives as α-glucosidase inhibitors via CSI-mediated amination reaction

Abstract

Concise synthesis of ent-conduramine C-1 and its derivatives has been achieved by using commercially available d-ribose. The key steps in the synthesis are regioselective and diastereoselective amination of polybenzyl ethers by chlorosulfonyl isocyanate (CSI), chelation-controlled carbonyl addition, and intramolecular olefin metathesis. All of the synthesized compounds were evaluated for inhibitory activity against α-glucosidase. The derivatives 18 (IC₅₀ = 0.65 ± 0.03 mM) and 19 (IC₅₀ = 0.26 ± 0.01 mM) were identified to be more potent than well-known α-glucosidase inhibitor acarbose (IC₅₀ = 1.05 ± 0.17 mM) as a positive control.

Keywords: Amination; Chlorosulfonyl isocyanate; Conduramine; α-Glucosidase inhibitor.